On Damping and Fluidelastic Instability in a Tube Bundle Subjected to Two-Phase Cross-Flow

An experimental study was conducted to investigate damping and uidelastic instability in tube arrays subjected to twophase cross-ow. The purpose of this research was to improve our understanding of these phenomena and how they are affected by void fraction and ow regime. The working uid used was Freon 11, which better models steam-water than air-water mixtures in terms of vapour-liquid mass ratio as well as permitting phase changes due to pressure uctuations. The damping measurements were obtained by plucking the monitored tube from outside the test section using electromagnets. An exponential function was tted to the tube decay trace, producing consistent damping measurements and minimizing the effect of frequency shifting due to uid added mass uctuations. The void fraction was measured using a gamma densitometer, introducing an improvement over the Homogeneous Equilibrium Model (HEM) in terms of density and velocity predictions. It was found that the Capillary number, when combined with the total damping ratio (interfacial damping), shows a well dened behaviour depending on the ow regime. This observation can be used to develop a better methodology to normalize damping results. The uidelastic results agree with previously presented data when analyzed using the HEM and the half-power bandwidth method. The interfacial velocity is suggested for uidelastic studies due to its capability for collapsing the uidelastic data. The interfacial damping was introduced as a tool to include the effects of ow regime into the stability maps

Damping Measurements In Tube Bundles Subjected To Two-phase Cross Flow

An experimental study was conducted to investigate twophase damping in tube arrays. The objective was to compare different measurement methodologies in order to obtain a more reliable damping estimate. This will allow for improved guidelines related to failures due to fluidelastic instability in tube bundles. The methods compared were the traditionally used halfpower bandwidth, the logarithmic decrement and an exponential fitting to the tube decay response. The working fluid used was Refrigerant 11 (Freon), which better models the real steamwater problem, as it allows for phase change. The void fraction was measured using a gamma densitometer, introducing an improvement over the traditional Homogeneous Equilibrium Model (HEM) in terms of velocity and density predictions. The results obtained by using the half-power bandwidth method agree with data previously reported for two-phase flow. The experiments showed that the half-power bandwidth produces higher damping values than the other two, but only up to a certain void fraction. After that point, the results obtained from the three methods are very similar. The exponential fitting proved to be more consistent than the logarithmic decrement, and it is not as sensitive as the half-power bandwidth to the frequency shifting caused by the change in added mass around the tube. By plotting the damping ratio as a function of void fraction, pitch mass flux and flow regime, we were able to verify that damping is more dependent on void fraction and flow regime than on mass flux

Identification of Small Molecule Inhibitors of Clostridium perfringens ε-Toxin Cytotoxicity Using a Cell-Based High-Throughput Screen

The Clostridium perfringens epsilon toxin, a select agent, is responsible for a severe, often fatal enterotoxemia characterized by edema in the heart, lungs, kidney, and brain. The toxin is believed to be an oligomeric pore-forming toxin. Currently, there is no effective therapy for countering the cytotoxic activity of the toxin in exposed individuals. Using a robust cell-based high-throughput screening (HTS) assay, we screened a 151,616-compound library for the ability to inhibit ε-toxin-induced cytotoxicity. Survival of MDCK cells exposed to the toxin was assessed by addition of resazurin to detect metabolic activity in surviving cells. The hit rate for this screen was 0.6%. Following a secondary screen of each hit in triplicate and assays to eliminate false positives, we focused on three structurally-distinct compounds: an N-cycloalkylbenzamide, a furo[2,3-b]quinoline, and a 6H-anthra[1,9-cd]isoxazol. None of the three compounds appeared to inhibit toxin binding to cells or the ability of the toxin to form oligomeric complexes. Additional assays demonstrated that two of the inhibitory compounds inhibited ε-toxin-induced permeabilization of MDCK cells to propidium iodide. Furthermore, the two compounds exhibited inhibitory effects on cells pre-treated with toxin. Structural analogs of one of the inhibitors identified through the high-throughput screen were analyzed and provided initial structure-activity data. These compounds should serve as the basis for further structure-activity refinement that may lead to the development of effective anti-ε-toxin therapeutics

Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration

Brain aging is associated with diminished circadian clock output and decreased expression of the core clock proteins, which regulate many aspects of cellular biochemistry and metabolism. The genes encoding clock proteins are expressed throughout the brain, though it is unknown whether these proteins modulate brain homeostasis. We observed that deletion of circadian clock transcriptional activators aryl hydrocarbon receptor nuclear translocator-like (Bmal1) alone, or circadian locomotor output cycles kaput (Clock) in combination with neuronal PAS domain protein 2 (Npas2), induced severe age-dependent astrogliosis in the cortex and hippocampus. Mice lacking the clock gene repressors period circadian clock 1 (Per1) and period circadian clock 2 (Per2) had no observed astrogliosis. Bmal1 deletion caused the degeneration of synaptic terminals and impaired cortical functional connectivity, as well as neuronal oxidative damage and impaired expression of several redox defense genes. Targeted deletion of Bmal1 in neurons and glia caused similar neuropathology, despite the retention of intact circadian behavioral and sleep-wake rhythms. Reduction of Bmal1 expression promoted neuronal death in primary cultures and in mice treated with a chemical inducer of oxidative injury and striatal neurodegeneration. Our findings indicate that BMAL1 in a complex with CLOCK or NPAS2 regulates cerebral redox homeostasis and connects impaired clock gene function to neurodegeneration

An injectable bone marrow-like scaffold enhances T cell immunity after hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for multiple disorders, but deficiency and dysregulation of T cells limit its utility. Here we report a biomaterial-based scaffold that mimics features of T cell lymphopoiesis in the bone marrow. The bone marrow cryogel (BMC) releases bone morphogenetic protein-2 to recruit stromal cells and presents the Notch ligand Delta-like ligand-4 to facilitate T cell lineage specification of mouse and human hematopoietic progenitor cells. BMCs subcutaneously injected in mice at the time of HSCT enhanced T cell progenitor seeding of the thymus, T cell neogenesis and diversification of the T cell receptor repertoire. Peripheral T cell reconstitution increased ~6-fold in mouse HSCT and ~2-fold in human xenogeneic HSCT. Furthermore, BMCs promoted donor CD4+ regulatory T cell generation and improved survival after allogeneic HSCT. In comparison to adoptive transfer of T cell progenitors, BMCs increased donor chimerism, T cell generation and antigen-specific T cell responses to vaccination. BMCs may provide an off-the-shelf approach for enhancing T cell regeneration and mitigating graft-versus-host disease in HSCT

Serum Bovine Immunoglobulins Improve Inflammation and Gut Barrier Function in Persons with HIV and Enteropathy on Suppressive ART.

BackgroundSystemic inflammation persists in chronic HIV infection and is associated with increased rates of non-AIDS events such as cardiovascular and liver disease. Increased gut permeability and systemic exposure to microbial products are key drivers of this inflammation. Serum-derived bovine immunoglobulin/protein isolate (SBI) supports gut healing in other conditions such as inflammatory bowel disease.MethodsIn this randomized, double-blind study, participants receiving suppressive antiretroviral therapy (ART) with chronic diarrhea received placebo or SBI at 2.5 g BID or 5 g BID for 4 weeks, followed by a 20-week placebo-free extension phase with SBI at either 2.5 or 5 g BID. Intestinal fatty acid binding protein (I-FABP), zonulin, flagellin, lipopolysaccharide (LPS) and LPS-binding protein, and inflammatory markers were measured by ELISA or multiplex assays. Non-parametric tests were used for analysis.ResultsOne hundred three participants completed the study. By week 24 SBI significantly decreased circulating levels of I-FABP (-0.35 ng/μL, P=0.002) and zonulin (-4.90 ng/μL, P=0.003), suggesting improvement in gut damage, and interleukin-6 (IL-6) (-0.40 pg/μL, P=0.002), reflecting improvement in systemic inflammation. In participants with the lowest quartile of CD4+ T-cell counts at baseline (189-418 cells/μL), CD4+ T-cell counts increased significantly (26 cells/μL; P=0.002).ConclusionsOral SBI may decrease inflammation and warrants further exploration as a potential strategy to improve gut integrity and decrease systemic inflammation among persons receiving prolonged suppressive ART

Exploring the impact of pediatric short bowel syndrome on parent well‐being using a disease‐specific pilot survey

Background: Children with short bowel syndrome (SBS) have complex care needs, most of which are met in the home by family caregivers who may experience a range of stressors unique to this experience. Prior research suggests that parents of children with SBS have poorer health‐related quality of life than peers parenting children without health needs, but the mechanisms shaping parent outcomes are understudied. Methods: A pilot survey was developed using a community‐driven research design to measure the impact of disease‐specific items on parent‐perceived well‐being. The cross‐sectional survey, which included both closed‐ended and open‐ended items, was distributed to a convenience sample of parents of children with SBS. Quantitative and qualitative data were integrated for a mixed‐methods analysis of how individual items impacted parent well‐being. Results: Twenty parents completed the survey. Sleep interruptions, lack of support and resources, and psychological stressors and their mental health implications were more frequently reported as stressors than logistics related to caregiving (e.g., managing therapies and preparing specialized meals). Conclusion: The impact of a child\u27s SBS on parent well‐being may stem mainly from three interconnected domains: poor sleep and its consequences, lack of access to support and resources, and a range of psychological stressors that affect parent mental health. Understanding the mechanisms through which SBS shapes parent well‐being is a necessary first step for developing targeted interventions to support parents and provide family‐centered care

Exploring the impact of pediatric short bowel syndrome on parent well‐being using a disease‐specific pilot survey

Background: Children with short bowel syndrome (SBS) have complex care needs, most of which are met in the home by family caregivers who may experience a range of stressors unique to this experience. Prior research suggests that parents of children with SBS have poorer health‐related quality of life than peers parenting children without health needs, but the mechanisms shaping parent outcomes are understudied. Methods: A pilot survey was developed using a community‐driven research design to measure the impact of disease‐specific items on parent‐perceived well‐being. The cross‐sectional survey, which included both closed‐ended and open‐ended items, was distributed to a convenience sample of parents of children with SBS. Quantitative and qualitative data were integrated for a mixed‐methods analysis of how individual items impacted parent well‐being. Results: Twenty parents completed the survey. Sleep interruptions, lack of support and resources, and psychological stressors and their mental health implications were more frequently reported as stressors than logistics related to caregiving (e.g., managing therapies and preparing specialized meals). Conclusion: The impact of a child\u27s SBS on parent well‐being may stem mainly from three interconnected domains: poor sleep and its consequences, lack of access to support and resources, and a range of psychological stressors that affect parent mental health. Understanding the mechanisms through which SBS shapes parent well‐being is a necessary first step for developing targeted interventions to support parents and provide family‐centered care